An electronic pressure-meter nociception paw test for rats

Vivancos, Gustavo Gameiro; Verri, Waldiceu A.; Cunha, Thiago M.; Schivo, Ieda R. S.; Parada, Carlos A.; Cunha, Fernando Q.; Ferreira, Sérgio Henrique

doi:10.1590/s0100-879x2004000300017

Cited by 201 publications

(136 citation statements)

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“…Electronic pressure-meter test. Mechanical hypernociception was tested in mice (20-30 g) and rats as previously reported (35,36). In a quiet room, mice or rats were placed in acrylic cages with wire-grid floors.…”

Section: Animalsmentioning

confidence: 99%

Morphine peripheral analgesia depends on activation of the PI3Kγ/AKT/nNOS/NO/K _ATP signaling pathway

Cunha

Roman‐Campos

Lotufo

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

188

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Morphine is one of the most prescribed and effective drugs used for the treatment of acute and chronic pain conditions. In addition to its central effects, morphine can also produce peripheral analgesia. However, the mechanisms underlying this peripheral action of morphine have not yet been fully elucidated. Here, we show that the peripheral antinociceptive effect of morphine is lost in neuronal nitric-oxide synthase null mice and that morphine induces the production of nitric oxide in primary nociceptive neurons. The activation of the nitric-oxide pathway by morphine was dependent on an initial stimulation of PI3Kγ/AKT protein kinase B (AKT) and culminated in increased activation of K ATP channels. In the latter, this intracellular signaling pathway might cause a hyperpolarization of nociceptive neurons, and it is fundamental for the direct blockade of inflammatory pain by morphine. This understanding offers new targets for analgesic drug development.M orphine is one of the most prescribed and effective drugs used for treatment of postoperatory and acute severe pain. Nevertheless, its use is frequently limited by undesirable side effects including respiratory depression, tolerance, and addiction. The discovery that morphine can also produce peripheral analgesia in the setting of inflammatory pain opened the possibility of developing peripheral restricted opioids devoid of central side effects (1).Morphine peripheral analgesia was discovered by its direct effect on already established inflammatory hypernociception induced by prostaglandin E 2 (PGE 2 ) injected in rat hind paws (1). Therefore, in contrast to aspirin-like drugs whose analgesic mechanism depends on prevention of nociceptor sensitization by inhibiting synthesis of prostaglandins, opioids are able to directly block ongoing nociceptor sensitization. However, the molecular mechanisms triggered by morphine to promote this action have not been fully elucidated. The present study reports on a series of experiments using behavioral, biochemical, and electrophysiological approaches to address this issue. The following major findings are reported herein: (i) the activation of peripheral opioid receptors in primary nociceptive neurons by morphine triggers a cascade of intracellular signaling events initiated by PI3Kγ/Protein kinase B (AKT); (ii) this is accompanied by activation of neuronal nitric oxide synthase (nNOS) and nitric oxide (NO) production, which (iii) induces an increase in K ATP channel currents; and (iv) it causes a hyperpolarization of nociceptive neurons. Results and DiscussionBased on the evidence that cAMP was the key intracellular second messenger involved in PGE 2 -induced nociceptor sensitization (2) and that opioid-receptor activation in vitro was coupled to adenylyl-cyclase inhibition (3), it was initially suggested that these drugs counteracted inflammatory hypernociception directly through inhibition of PGE 2 -induced adenylyl-cyclase activation (1, 4). Subsequent in vitro studies, which confirmed the ability of opioids to inhibit ad...

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Section: Animalsmentioning

confidence: 99%

Morphine peripheral analgesia depends on activation of the PI3Kγ/AKT/nNOS/NO/K _ATP signaling pathway

Cunha

Roman‐Campos

Lotufo

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

188

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“…Mechanical hyperalgesia was measured by the electronic von Frey method [23]. In a quiet room, rats were placed in acrylic cages (12 9 20 9 17 cm) with wire grid floors, 15-30 min before the beginning of the tests.…”

Section: Electronic Von Freymentioning

confidence: 99%

Cytokine inhibition and time-related influence of inflammatory stimuli on the hyperalgesia induced by the nucleus pulposus

2011

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Introduction The symptoms of lumbar disc herniation, such as low back pain and sciatica, have been associated with local release of cytokines following the inflammatory process induced by the contact of the nucleus pulposus (NP) with the spinal nerve. Material and methods Using an animal experimental model of intervertebral disc herniation and behavioral tests to evaluate mechanical (electronic von Frey test) and thermal (Hargreaves Plantar test) hyperalgesia in the hind paw of rats submitted to the surgical model, this study aimed to detect in normal intervertebral disc the cytokines known to be involved in the mechanisms of inflammatory hyperalgesia, to observe if previous exposure of the intervertebral disc tissue to specific antibodies could affect the pain behavior (mechanical and thermal hyperalgesia) induced by the NP, and to observe the influence of the time of contact of the NP with the fifth lumbar dorsal root ganglion (L5-DRG) in the mechanical and thermal hyperalgesia. Results The cytokines present at highest concentrations in the rat NP were TNF-a, IL-1b and CINC-1. Rats submitted to the disc herniation experimental model, in which a NP from the sacrococcygeal region is deposited over the right L5-DRG, showed increased mechanical and thermal hyperalgesia that lasted at least 7 weeks. When the autologous NP was treated with antibodies against the three cytokines found at highest concentrations in the NP (TNF-a, IL-1b and CINC-1), there was decrease in both mechanical and thermal hyperalgesia in different time points, suggesting that each cytokine may be important for the hyperalgesia in different steps of the inflammatory process. The surgical remotion of the NP from herniated rats 1 week after the implantation reduced the hyperalgesia to the level similar to the control group. This reduction in the hyperalgesia was also observed in the group that had the NP removed 3 weeks after the implantation, although the intensity of the hyperalgesia did not decreased totally. The removal of the NP after 5 weeks did not changed the hyperalgesia observed in the hind paw, which suggests that the longer the contact of the NP with the DRG, the greater is the possibility of development of chronic pain. Conclusion Together our results indicate that specific cytokines released during the inflammatory process induced by the herniated intervertebral disc play fundamental role in the development of the two modalities of hyperalgesia (mechanical and thermal) and that the maintenance of this inflammation may be the most important point for the chronification of the pain.

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“…So, we decided to carry out the first evaluation 15 minutes after injury, avoiding evaluating in the quiescent period, with new evaluation 30 and 60 minutes after, aiming at observing nociceptive and edema behavior along 1h after injury. Evaluation with Von Frey filament provides sensitive, objective and quantifiable nociceptive measures 12 , and edema formation measurement using the caliper is also presented by the literature 13 . Considering that evaluators were experienced and animals were trained before evaluations, presented data are reliable, showing that there have been no changes in edema formation with the use of ultrasound, producing neither increase nor decrease, since it has been used during acute irritation stage.…”

Section: Discussionmentioning

confidence: 99%

Comparison of continuous and pulsed ultrasound therapy in knee hyperalgesia of Wistar rats

Bertolini¹,

Coradini²,

Kunz³

et al. 2014

Revista Dor

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BACKGROUND AND OBJECTIVES:Among electro agents ultrasound is one of the most common, however, there is insufficient evidence of the beneficial effects with the parameters currently used. The aim of this study was to compare the effect of continuous and pulsed ultrasound therapy on experimental hyperalgesia and edema in knees of Wistar rats. METHODS: 18 rats were divided into three groups: CG-control group; GUP -treated with pulsed ultrasound 50%; and GUC -continuous ultrasound. To accomplish the lesion, animals were manually restrained and 100µL of 5% formalin solution were injected into the right tibiofemoral space. For assessment of nociception digital Von Frey filament was used on the medial side of the joint, until clinching. Edema was evaluated with mid-lateral knee caliper. Assessments occurred in the preinjury (EV1), after 15 (EV2), 30 (EV3) and 60 (EV4) minutes of the injury. After EV2, treatment was initiated with ultrasound with 0.4W/cm 2 (SATA), pulsed or continuous. RESULTS:The CG had hypernociception, with no return to baseline. GUP has returned to baseline as from EV3 and for continuous ultrasound in EV4. All three groups showed similar behavior for edema, with onset in EV2, without reduction. CONCLUSION: Therapeutic ultrasound was effective to decrease nociception, and the pulsed form showed early results, however, both forms of application had no effect on the formation and maintenance of acute edema. Keywords: Edema, Pain measurement, Ultrasound therapy. Comparison of continuous and pulsed ultrasound therapy in knee hyperalgesia of Wistar rats* RESUMO JUSTIFICATIVA E OBJETIVOS:Dentre os agentes eletrotér-micos o ultrassom é um dos mais comuns, contudo, há insuficiente evidência dos efeitos benéficos com os parâmetros correntemente utilizados. Assim, o objetivo deste estudo foi comparar o efeito do ultrassom terapêutico contínuo e pulsado sobre hiperalgesia e edema experimentais em joelhos de ratos Wistar. MÉTODOS: Foram utilizados 18 ratos, divididos em três grupos: GC -grupo controle; GUP -tratado com ultrassom pulsado 50%; e, GUC -ultrassom contínuo. Para realizar a lesão, os animais foram contidos manualmente e 100µL de solução de formalina a 5% foram injetados no espaço tíbio-femoral direito. Para avaliação da nocicepção foi utilizado o filamento de Von Frey digital, na face medial da articulação, até a retirada do membro. A avaliação do edema foi realizada com paquimetria médio-lateral ao joelho. As avaliações ocorreram no momento pré-lesão (AV1), após 15 (AV2), 30 (AV3) e 60 (AV4) minutos da lesão. Após AV2, foi iniciado o tratamento com ultrassom com 0,4W/ cm² (SATA), de forma pulsada ou contínua. RESULTADOS: Para GC, houve a presença de hipernocicepção, sem retorno aos valores basais. Para GUP houve retorno aos valores basais a partir de AV3 e para o ultrassom contínuo em AV4. Para o edema, os três grupos apresentaram comportamento semelhante, com formação em AV2, sem redução posterior. CONCLUSÃO: O ultrassom terapêutico mostrou-se eficaz para redução do quadro nociceptivo, sen...

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An electronic pressure-meter nociception paw test for rats

Cited by 201 publications

References 31 publications

Morphine peripheral analgesia depends on activation of the PI3Kγ/AKT/nNOS/NO/K _ATP signaling pathway

Morphine peripheral analgesia depends on activation of the PI3Kγ/AKT/nNOS/NO/K _ATP signaling pathway

Cytokine inhibition and time-related influence of inflammatory stimuli on the hyperalgesia induced by the nucleus pulposus

Comparison of continuous and pulsed ultrasound therapy in knee hyperalgesia of Wistar rats

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An electronic pressure-meter nociception paw test for rats

Cited by 201 publications

References 31 publications

Morphine peripheral analgesia depends on activation of the PI3Kγ/AKT/nNOS/NO/K ATP signaling pathway

Morphine peripheral analgesia depends on activation of the PI3Kγ/AKT/nNOS/NO/K ATP signaling pathway

Cytokine inhibition and time-related influence of inflammatory stimuli on the hyperalgesia induced by the nucleus pulposus

Comparison of continuous and pulsed ultrasound therapy in knee hyperalgesia of Wistar rats

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Morphine peripheral analgesia depends on activation of the PI3Kγ/AKT/nNOS/NO/K _ATP signaling pathway

Morphine peripheral analgesia depends on activation of the PI3Kγ/AKT/nNOS/NO/K _ATP signaling pathway